DNA methylation is recognized as a principal contributor to the stability of gene expression in development and to the maintenance of cellular identity (Bird, 2002; Cedar and Bergman, 2012; Jaenisch and Bird, 2003; Reik et al., 2001). A variety of methods for measuring DNA methylation are available. These include digestion of DNA with methylation-sensitive restriction enzymes, affinity-based enrichment and sequencing of DNA fragments containing methylated cytosine, and chemical conversion methods. A widely used chemical conversion method relies on the fact that treatment of DNA with bisulfite converts cytosine to uracil but leaves 5-methylcytosine intact. Thus, 5-methylcytosine patterns can be mapped by treating DNA with bisulfite, followed by sequencing. Microarray analysis (e.g., using the Illumina 450K Human Methylation array) of bisulfite-treated DNA has also been extensively used in studying methylation.
Recent advances in sequencing technologies have allowed the establishment of methylation maps from multiple cell types in both human (Ziller et al., 2013) and mouse (Hon et al., 2013). However, changes in DNA methylation are dynamic, and it is still largely unknown how epigenomic information dictates spatial and temporal gene expression programs (Smith and Meissner, 2013).